6-158111155-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032861.4(SERAC1):c.*211T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 390,260 control chromosomes in the GnomAD database, including 21,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8299 hom., cov: 32)
  • Exomes 𝑓: 0.33 (13413 hom.)
• Consequence: SERAC1 NM_032861.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.485

Genes affected

SERAC1 (HGNC:21061): (serine active site containing 1) The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-158111155-A-G is Benign according to our data. Variant chr6-158111155-A-G is described in ClinVar as [Benign]. Clinvar id is 1282099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERAC1	NM_032861.4	c.*211T>C		3_prime_UTR_variant	17/17	ENST00000647468.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERAC1	ENST00000647468.2	c.*211T>C		3_prime_UTR_variant	17/17		NM_032861.4	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49807 AN: 151956 Hom.: 8295 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.330 AC: 78647 AN: 238186 Hom.: 13413 Cov.: 4 AF XY: 0.327 AC XY: 40218 AN XY: 122942

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.328 AC: 49832 AN: 152074 Hom.: 8299 Cov.: 32 AF XY: 0.327 AC XY: 24335 AN XY: 74344

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.309

Alfa AF: 0.332 Hom.: 13985

Bravo AF: 0.316

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2502606; hg19: chr6-158532187; COSMIC: COSV65597598; COSMIC: COSV65597598;